Regulation of rat heme oxygenase-1 expression by interleukin-6 via the Jak/STAT pathway in hepatocytes. Export

@article{citeulike:711388, abstract = {BACKGROUND/AIMS: Heme oxygenase-1 (HO-1) can be induced by various stimuli, one of which is interleukin-6 (IL-6). Therefore, the aim of this study was to elucidate the molecular mechanisms responsible for IL-6-dependent HO-1 induction in the liver. METHODS: The IL-6-dependent HO-1 regulation in rat primary hepatocytes and HepG2 hepatoma cells was studied by Northern and Western blot analyses, HO-1 promoter reporter gene assays and EMSA. RESULTS: The HO-1 expression was transcriptionally induced by IL-6 in a time- and dose-dependent manner. Activation of signal transducers and activators of transcription (STAT) factors by the IL-6 receptor was crucial for HO-1 induction. By contrast, negative regulation of HO-1 expression appeared to be mediated through the SH2-domain-containing tyrosine phosphatase-2 (SHP2)/ suppressors of cytokine signaling-3 (SOCS3) binding site within the gp130 IL-6 receptor subunit. Among the three putative STAT binding elements (SBE) in the HO-1 promoter, only the distal one was functional and when deleted, the remaining Luc induction was completely obliterated by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. CONCLUSIONS: The HO-1 SBE3 mediates HO-1 gene induction by IL-6 mainly via activation of the Jak/STAT pathway.}, address = {Abteilung Gastroenterologie und Endokrinologie, Uniklinikum, Georg-August-Universit\"{a}t G\"{o}ttingen, D-37075 G\"{o}ttingen, Germany.}, author = {Tron, K. and Samoylenko, A. and Musikowski, G. and Kobe, F. and Immenschuh, S. and Schaper, F. and Ramadori, G. and Kietzmann, T.}, citeulike-article-id = {711388}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.jhep.2005.12.019}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16510205}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16510205}, doi = {10.1016/j.jhep.2005.12.019}, issn = {0168-8278}, journal = {J Hepatol}, keywords = {heme-oxygenase}, month = {July}, number = {1}, pages = {72--80}, posted-at = {2006-06-26 15:34:00}, priority = {2}, title = {Regulation of rat heme oxygenase-1 expression by interleukin-6 via the Jak/STAT pathway in hepatocytes.}, url = {http://dx.doi.org/10.1016/j.jhep.2005.12.019}, volume = {45}, year = {2006} }

TY - JOUR ID - citeulike:711388 L3 - citeulike-article-id:711388 N2 - BACKGROUND/AIMS: Heme oxygenase-1 (HO-1) can be induced by various stimuli, one of which is interleukin-6 (IL-6). Therefore, the aim of this study was to elucidate the molecular mechanisms responsible for IL-6-dependent HO-1 induction in the liver. METHODS: The IL-6-dependent HO-1 regulation in rat primary hepatocytes and HepG2 hepatoma cells was studied by Northern and Western blot analyses, HO-1 promoter reporter gene assays and EMSA. RESULTS: The HO-1 expression was transcriptionally induced by IL-6 in a time- and dose-dependent manner. Activation of signal transducers and activators of transcription (STAT) factors by the IL-6 receptor was crucial for HO-1 induction. By contrast, negative regulation of HO-1 expression appeared to be mediated through the SH2-domain-containing tyrosine phosphatase-2 (SHP2)/ suppressors of cytokine signaling-3 (SOCS3) binding site within the gp130 IL-6 receptor subunit. Among the three putative STAT binding elements (SBE) in the HO-1 promoter, only the distal one was functional and when deleted, the remaining Luc induction was completely obliterated by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. CONCLUSIONS: The HO-1 SBE3 mediates HO-1 gene induction by IL-6 mainly via activation of the Jak/STAT pathway. IS - 1 JF - J Hepatol SN - 0168-8278 AD - Abteilung Gastroenterologie und Endokrinologie, Uniklinikum, Georg-August-Universität Göttingen, D-37075 Göttingen, Germany. EP - 80 TI - Regulation of rat heme oxygenase-1 expression by interleukin-6 via the Jak/STAT pathway in hepatocytes. VL - 45 SP - 72 KW - heme-oxygenase AU - Tron, K AU - Samoylenko, A AU - Musikowski, G AU - Kobe, F AU - Immenschuh, S AU - Schaper, F AU - Ramadori, G AU - Kietzmann, T PY - 2006/07// UR - http://dx.doi.org/10.1016/j.jhep.2005.12.019 ER -